Obesity, sedentariness and aging are associated with hyperlipidemia, glucose intolerance, and altered sympathoadrenal responsiveness. To determine the relationships among these variables, this study examines glucose and lipid metabolism and sympatho-adrenal function in obese, sedentary men aged 45-75 years at entry into the study and again after either weight reduction or aerobic training. The endocrine-metabolic functions being evaluated are: 1) insulin secretion and sensitivity assessed by euglycemic and hyperglycemic clamps; 2) lipoprotein metabolism by lipoprotein lipid profiles, high density lipoprotein (HDL) subspecies levels and lipoprotein lipase activity in postheparin plasma and adipose tissue; 3) the regulation of adipose tissue metabolism and fat cell size by fitness (V02max), fatness (% body fat) and the regional distribution of body fat (waist:hip circumferential ratio) by studying the responsiveness of adipose tissue from upper and lower body sites to beta-and alpha2- adrenergic stimuli; and 4) sympathoadrenal responses to upright posture, oral glucose, and hyperinsulinemia during a euglycemic clamp. A total of 132 subjects have completed baseline metabolic studies and have been randomized to either the weight reduction or aerobic exercise training interventions. At baseline these men have low levels of physical fitness, impaired glucose tolerance, increased insulin resistance, and low plasma levels of HDL cholesterol (HDL-C) when compared to age-matched, lean controls. Twenty subjects have completed the weight loss program and 14 the exercise program. With weight loss there was a significant improvement in a number of metabolic parameters with no change in their maximal aerobic capacity. In 9 subjects whose V02max increased greater than 15%, insulin sensitivity and HDL-C rose, triglyceride decreased and fat cell size got smaller, presumably due to an increase in stimulated lipolysis secondary to increased sensitivity to beta-adrenergic agonists. There are currently 25 subjects in the weight loss group, 20 in the exercise group, and 12 subjects are in various phases of baseline testing prior to randomization.